SUSTAIN - Study of Ranibizumab in Patients With Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration

A Phase IIIb, Open-label, Multi-center 12 Month Study to Evaluate the Safety, Tolerability and Efficacy of Ranibizumab (0.3 mg and/or 0.5 mg) in Patients With Subfoveal Choroidal Neovasculariza-tion Secondary to Age-related Macular Degeneration

Ranibizumab is a humanised recombinant monoclonal antibody fragment targeted against human vascular endothelial growth factor A. This study will assess the safety and efficacy of ranibizumab administered on an as-needed dosing regimen in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).

Study Overview

• Status: Completed
• Conditions: Age Related Macular Degeneration; Choroidal Neovascularization
• Intervention / Treatment: Drug: Ranibizumab

• Study Type: Interventional
• Enrollment (Actual): 531
• Phase: Phase 3

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland
    • Novartis - 64 sites in 11 countries

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Patients who participated in this study included those who had completed participation in the study CRFB002A2301 (ANCHOR; NCT00061594), newly diagnosed patients, as well as previously diagnosed patients who had had recent disease progression.

Inclusion Criteria:

• Male or female patients > 50 years of age
• Diagnosis of active primary or recurrent CNV secondary to AMD, including those with predominantly classic, minimally classic or occult lesions with no classic component
• The total area of CNV (including both classic and occult components) encompassed within the lesion must be >= 50% of the total lesion area
• The total lesion area must be <= 12 disc areas
• Patients who have a BCVA (best corrected visual acuity) score between 73 and 24 letters, inclusive, in the study eye using ETDRS-like (Early Treatment of Diabetic Retinopathy Study) grading charts (approximately 20/40 to 20/320)

Exclusion Criteria:

• Patients who have a BCVA of < 34 letters in both eyes (legally blind is defined as bilateral vision below 20/200 or less than 34 letters)
• Laser photocoagulation, treatment with intravitreal steroids, verteporfin photo dynamic therapy or pegaptanib sodium in the study eye within 30 days preceding Day 1
• Previous participation in a clinical trial (for either eye) involving anti-angiogenic drugs (pegaptanib, ranibizumab, anecortave acetate, protein kinase C inhibitors, etc.)

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ranibizumab; Ranibizumab-naïve (Non-ANCHOR) patients received up to 12 intravitreal injections (Month 0 through Month 11). The dose of 0.3 mg ranibizumab was administered monthly for three consecutive months. From Month 3 through Month 11, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab were injected as individually needed based on re-treatment criteria described in the protocol. For patients who had participated in the ANCHOR study, either 0.3 mg ranibizumab or, after implementation of an amendment to the protocol, 0.5 mg ranibizumab was injected if the patient met re-treatment criteria described in the protocol. Ranibizumab was administered no sooner than 14 days after the previous treatment.

Drug: Ranibizumab; Other Names: rhuFab V2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With Ocular Adverse Events (AEs) in the Study Eye	Percentage of patients with ocular adverse events in the study eye over the one year (12 month) treatment period.	Baseline through end of study (12 month treatment period)
Percentage of Patients With Targeted Grade 3 Adverse Events (AEs) in the Study Eye	Grade 3 targeted AEs included: 4+ ocular inflammation or 2-3+ ocular inflammation failing to decrease to ≤ 1+ within 30 days; ≥ 30 letter decrease in BCVA that developed within 14 days of ranibizumab injection; sustained (>15 minutes) loss of light perception due to elevated intraocular pressure (IOP) or a >20 mm Hg change in IOP persisting longer than 14 days; new retinal tear or detachment involving the macula; new vitreous hemorrhage >2+ severity not resolving within 14 days; new or increase of previous retinal hemorrhage >1 disc area in size and involving the fovea	Baseline through end of study (12 month treatment period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Best Corrected Visual Acuity (BCVA) of the Study Eye From Baseline to Month 3	BCVA was assessed using best correction determined from protocol refraction. BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at an initial testing distance of 4 meters. BCVA is measured by the number of letters a patient could correctly read on an eye chart; hence an increased score indicates improvement in acuity.	Baseline and Month 3
Mean Change in Best Corrected Visual Acuity (BCVA) of the Study Eye From Baseline to Month 12	BCVA was assessed using best correction determined from protocol refraction. BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at an initial testing distance of 4 meters. BCVA is measured by the number of letters a patient could correctly read on an eye chart; hence an increased score indicates improvement in acuity.	Baseline and Month 12
Mean Change in Central Retinal Thickness of the Study Eye From Baseline to Month 3	Central retinal thickness was assessed using optical coherence tomography (OCT). OCT imaging was performed by trained personnel at each site using the Zeiss Stratus OCT™ 3 with version A6.1 (or more recent) software. Analysis of the OCT images was performed by the investigator. A negative number indicates improvement (reduced thickness).	Baseline and Month 3
Mean Change in Central Retinal Thickness of the Study Eye From Baseline to Month 12	Central retinal thickness was assessed using optical coherence tomography (OCT). OCT imaging was performed by trained personnel at each site using the Zeiss Stratus OCT™ 3 with version A6.1 (or more recent) software. Analysis of the OCT images was performed by the investigator. A negative number indicates improvement (reduced thickness).	Baseline and Month 12
Time to the First Retreatment After Month 2	Time to first re-treatment is calculated as time difference in months starting from Month 2 until the month of first re-treatment. Criteria for re-treatment: a >5 letter decrease in BCVA (determined using EDRS charts) based upon the highest visual acuity score from any prior scheduled study visit (Months 0, 1, 2 or 3); a >100 µm increase in central retinal thickness (determined using OCT) from the thinnest measurement from any prior scheduled study visit (Months 0, 1, 2 or 3)	Month 2 to Month 11
Total Number of Treatments	Total number of treatments administered during the entire treatment period (Month 0 to 11).	Baseline (Month 0) to Month 11

Collaborators and Investigators

• Sponsor: Novartis
• Investigators: Study Chair: Novartis Customer Information, Novartis - Including Sites in Germany

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): April 1, 2008
• Study Completion: April 1, 2008

Study Registration Dates

• First Submitted: April 11, 2006
• First Submitted That Met QC Criteria: May 29, 2006
• First Posted (Estimate): May 31, 2006

Study Record Updates

• Last Update Posted (Estimate): February 18, 2011
• Last Update Submitted That Met QC Criteria: February 15, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: AMD, ranibizumab
• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Retinal Degeneration; Retinal Diseases; Uveal Diseases; Choroid Diseases; Metaplasia; Macular Degeneration; Choroidal Neovascularization; Neovascularization, Pathologic; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: CRFB002A2303